A biophysical study on the mechanism of interactions of DOX or PTX with ?-lactalbumin as a delivery carrier.

ABSTRACT: Doxorubicin and paclitaxel, two hydrophobic chemotherapeutic agents, are used in cancer therapies. Presence of hydrophobic patches and a flexible fold could probably make ?-Lactalbumin a suitable carrier for hydrophobic drugs. In the present study, a variety of thermodynamic, spectroscopic, computational, and cellular techniques were applied to assess ?-lactalbumin potential as a carrier for doxorubicin and paclitaxel. According to isothermal titration calorimetry data, the interaction between ?-lactalbumin and doxorubicin or paclitaxel is spontaneous and the K (M-1) value for the interaction of ?-lactalbumin and paclitaxel is higher than that for doxorubicin. Differential scanning calorimetry and anisotropy results indicated formation of ?-lactalbumin complexes with doxorubicin or paclitaxel. Furthermore, molecular docking and dynamic studies revealed that TRPs are not involved in ?-Lac's interaction with Doxorubicin while TRP 60 interacts with paclitaxel. Based on Pace analysis to determine protein thermal stability, doxorubicin and paclitaxel induced higher and lower thermal stability in ?-lactalbumin, respectively. Besides, fluorescence lifetime measurements reflected that the interaction between ?-lactalbumin with doxorubicin or paclitaxel was of static nature. Therefore, the authors hypothesized that ?-lactalbumin could serve as a carrier for doxorubicin and paclitaxel by reducing cytotoxicity and apoptosis which was demonstrated during our in vitro cell studies.

SUBMITTER: Delavari B 

PROVIDER: S-EPMC6255783 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature